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VIDEO: D. Allan Drummond on The Heat Shock Response as a Condensation Response


Senior Scientist, Dewpoint Therapeutics

Type Kitchen Table Talk

D. Allan Drummond, associate professor at the University of Chicago, joined the Dewpoint scientists and community for a fantastic seminar on November 2, as part of the Kitchen Table Talk series. Allan has been a professor since 2011, when he started his academic research lab as a Bauer Fellow at Harvard after completing his PhD at Caltech with Nobel Laureate Frances Arnold, where he studied protein evolution. 

Interestingly, Allan spent seven years at the prominent software company Trilogy, ultimately culminating as the director of HR where he had a real emphasis on mentorship, which he continues to foster in his own lab. There, Allan also continues to meld his knowledge of computation and protein evolution to ask and answer questions about organismal fitness with a variety of multidisciplinary techniques, from hardcore biophysical techniques to genetics. He gave an engaging talk about his lab’s work (see below), and we had an insightful discussion afterward. He was also kind enough to answer a lingering question via email; you can find that further below

D. Allan Drummond on The Heat Shock Response as a Condensation Response

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Bede Portz (00:00:01):
Hi, everybody. It’s a real pleasure to introduce Allan, who’s an associate professor at the University of Chicago in the department of Biochemistry and Molecular Biology where he has been since 2011. Prior to this, Allan was a Bauer Fellow at Harvard, where he studied for five years after completing his Ph.D. at Caltech with Nobel Laureate, Frances Arnold. Allan’s current research program is at once a departure from and an extension of his work prior to the establishment of his own group. And by that I mean previously, he used strictly computational methods, but now he has a wet lab. But some of the questions converge on evolution, which is sort of an ongoing theme of Allan’s work.

Bede Portz (00:00:44):
Specifically to condensates, what I feel has distinguished Allan’s group are two things. One, the multidisciplinary nature of his work. So, he has papers that, in single papers the methods span from hardcore biophysical techniques to genetics. And another emphasis, and I think distinguishing element of Allan’s research program, is an emphasis on function and really organismal fitness, which is perhaps the highest bar sort of measuring function.

Bede Portz (00:01:20):
Two more things about Allan that are interesting: Science was actually not his first career; he spent seven years at, what at the time was, a very prominent software company Trilogy, ultimately culminating as the director of HR where he had a real emphasis on mentorship. And that’s something that continues to this day. In fact, a number of people have left Allan’s lab and have gone on to start their own independent labs, and a number of folks have left his lab and are thriving in postdoctoral roles and elsewhere.

Bede Portz (00:01:53):
Not only is this not Allan’s first career, it’s also not his only career now. He’s also a very accomplished artist, particularly a sculptor, and he has exhibited these incredibly detailed sculptures of insects, both extant and extinct, in galleries. So, Allan is really a marvelous and well-rounded person. I really look forward to his talk today. If it has any of the enthusiasm and sort of curiosity that he’s exhibited in our conversations over the years, I’m sure his talk’s going to be excellent. So, welcome, Allan. Thanks for being here.

D. Allan Drummond (00:02:30):
Well, thank you so much for that, Bede. That is incredibly kind, and everyone should know that I’ve known Bede for many years now. We’ve been actually in each other’s orbits for many years now. And from the minute I met him, there was this sort of instant likability and connection and also scientific respect that has continued to develop over the years. So, we are constantly going back and forth on DMs on Twitter, and it’s lovely to finally see you quasi in person. Thanks, Jill, and thanks to all of you for the invitation here. This should be fun. I hope I can live up to the introduction.

D. Allan Drummond (00:03:11):
The idea here is going to be to try to convince you that one of the most well-studied “stress responses” across the entire tree of life, but, of course, many of us know it mostly from eukaryotes, has really been looked at through a lens that is not quite as productive as it could be, and that once you recognize that what is happening to cells during these sort of stress responses involves condensation, you start to reframe the entire problem in a way that really opens up a whole new set of vistas, I think, are biologically important, that can be inspiring for how we think about biological systems, and also potentially can change the way that we try to manipulate, perturb these systems…


Question from David Dachille: One thing you mentioned in your talk was that at different temperatures, the distribution of different condensates will vary. Does this imply an optimal temperature for each condensate mediated function? Does the proportion of a condensate within the condensate population dictate a function? And lastly, is there an optimal temperature for each condensate mediated function?
It was a really interesting talk got really got me thinking about condensate mechanisms!
Allan’s Response: It’s an interesting question. We think — based on results showing that the same protein condenses at different temperatures in organisms adapted to different thermal niches — that condensation does not have an “optimal temperature” so much as that individual proteins have evolved to condense at a temperature which has the same evolutionary significance. E.g. heat shock for a cryophile might be 32C, whereas for a thermophile it might be 50C, and homologous proteins in each organism would condense at the respective temperatures. Condensation, like so many other molecular properties, is an evolvable trait. Consequently, functions associated with condensation are not tied to any particular temperature. To the questions of whether the proportion of a condensate within a population dictates function, if I understand correctly, generally if condensation itself has a functional meaning (not guaranteed in every case!) then one would expect a relationship between proportion condensed and function — though this could be more function, less function, or some non-monotonic relationship! The functional repertoire of condensates is barely explored at this point, despite considerable creative thinking by many folks. Much to do.

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